Search

Activation of the blood coagulation cascade leads to fibrin deposition and platelet activation that are required for hemostasis. However, aberrant activation of coagulation can lead to thrombosis. Thrombi can cause tissue ischemia, and fibrin degradation products and activated platelets can enhance inflammation. In addition, coagulation proteases activate cells by cleavage of PARs (protease-activated receptors), including PAR1 and PAR2. Direct oral anticoagulants have recently been developed to specifically inhibit the coagulation proteases FXa (factor Xa) and thrombin. Administration of these inhibitors to wild-type mice can be used to determine the roles of FXa and thrombin in different inflammatory diseases. These results can be compared with the phenotypes of mice with deficiencies of either Par1 (F2r) or Par2 (F2rl1). However, inhibition of coagulation proteases will have effects beyond reducing PAR signaling, and a deficiency of PARs will abolish signaling from all proteases that activate these receptors. We will summarize studies that examine the roles of coagulation proteases, particularly FXa and thrombin, and PARs in different mouse models of inflammatory disease. Targeting FXa and thrombin or PARs may reduce inflammatory diseases in humans.

ObjectiveOvarian clear cell carcinoma (OCCC) and high grade serous ovarian cancer (HGSOC) are associated with the highest risk of VTE among patients with epithelial ovarian cancer (EOC). Tissue factor (TF) is a transmembrane glycoprotein which can trigger thrombosis. We sought to evaluate if there is an association between VTE and tumor expression of tissue factor (TF), plasma TF, and microvesicle TF (MV TF) activity in this high-risk population.MethodsWe performed a case-control study of OCCC and HGSOC patients with and without VTE. 105 patients who underwent surgery at a tertiary care center between January 1995 and October 2013 were included. Plasma TF was measured with an enzyme-linked immunosorbent assay. A TF-dependent Factor Xa generation assay was used to measure MV TF activity. Immunohistochemical (IHC) analysis was performed to evaluate tumor expression of TF.Results35 women with OCCC or HGSOC diagnosed with VTE within 9months of surgery were included in the case group. Those with VTE had a worse OS, p

Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Summary: Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection.

To evaluate the use of blueberry juice as an oral contrast agent in magnetic resonance (MR) imaging.MR imaging of phantoms of blueberry juice and of manganese chloride solutions with different manganese concentrations were conducted. Patient trials were conducted to evaluate manganese blood levels and signal intensity changes on MR images of the abdomen. T1- and T2-weighted conventional spin-echo MR imaging was performed at various field strengths. Six radiologists graded image contrast; signal intensities were calculated.T1 and T2 relaxation curves for blueberry juice and manganese chloride showed similar signal intensity profiles as a function of manganese concentration. Blood concentrations of manganese were unchanged before and after an oral dose of blueberry juice that contained 18 mg of manganese. The results of patient studies indicated that the optimal oral dose of manganese in blueberry juice was 3-4 mg/dL. T1 and T2 shortening were apparent at field strengths of 0.2-1.5 T.At appropriate concentrations, blueberry juice has the potential to be an effective oral contrast agent for MR imaging.

We retrospectively examined the MR imaging (MRI) findings in 144 patients with epilepsy (31 with temporal lobe epilepsy and 113 with other epilepsies). 110 cases (76.4%) showed abnormal findings such as spotty lesions in white matter, hippocampal atrophy and/or signal change, ventricular dilatation and/or deformity, developmental lesions, brain tumors and so on. Hippocampal atrophy and/or signal change was shown in 74.1% of temporal lobe epilepsy, a remarkably high percentage (P0.01) compared with the other types of epilepsies (18.1%). This finding means that hippocampal lesions may play a large part in the cause of temporal lobe epilepsy. Investigation of the relationship between clinical term and abnormal findings revealed that the longer the clinical term, the larger the number of hippocampal lesions, regardless of whether it is temporal lobe epilepsy or not. Thus hippocampal lesions may occur as a result of hypoxia accompanied with seizure. Therefore we recommend horizontal and/or vertical sections of hippocampus in MR imaging of all patients with epilepsy. Even though MR findings may reflect some secondary lesions, MRI will shed some light on the proper understanding of epilepsy.